The details of the dissolution of lignin at the molecular level in certain ionic liquids (ILs), such as cholinium-based ILs, are a relatively under-explored area and several key details to understanding the mechanism of dissolution remain to be discovered. To understand, answer, and connect the missing links in the delignification mechanism during biomass pretreatment with cholinium-based ILs, we use guiding factors such as Screening MODel for Real Solvents (COSMO-RS) and Molecular Dynamics Simulations (MD) to understand the interactions between lignin- such as model compounds and the anion and cation of several cholinium-based ILs. First, the lignin dissolution was investigated for cholinium-based ILs that contain five different carboxylate anions ([For] , [Ace] , [But] , [Hex] , and [Oct] ) and were compared to lysinate as the anion. The microscopic properties such as interaction energies, activity coefficient, radial and spatial distribution functions (RDF / SDF) and hydrogen bonds and their dynamics were assessed to characterize the lignin dissolution in these ILs and have been validated with experimental data. Among the anions investigated, both octanoate and lysinate-containing ILs showed better lignin dissolution; Lysinate is the best. The simulation data suggested that [Ch] [Lys] has a higher affinity for ether bonds of lignin (e.g., β-O-4) than for C – C linkages, indicating the higher delignification of hardwood and grass biomass (60–80% C – O – C linkages) in. explained [Ch] [Lys] .